title: Cyclo-oxygenase-2 expression is associated with vascular endothelial growth factor C expression and lymph node metastasis in oral squamous cell carcinoma.
abstract: OBJECTIVE
  Cervical lymph node metastasis in oral squamous cell carcinoma (OSCC) is recognized as a poor prognostic factor, although its mechanism remains unclear. Recently, cyclo-oxygenase-2 (COX-2) level has been found to correlate highly with vascular endothelial growth factor C (VEGF-C) and lymph node metastasis, as in other solid tumors. However, there has been no report of this correlation in OSCC. Therefore, the aim of this study was to investigate whether COX-2 immunohistochemical expression in OSCC was associated with VEGF-C expression, histopathologic parameters, and lymph node metastasis.
  
  
  METHODS
  Lymphatic vessel density, VEGF-C, and COX-2 immunohistochemical expression were examined pathologically in 60 specimens of invasive OSCC. Relations of histopathologic parameters to lymph node metastasis were analyzed.
  
  
  RESULTS
  Expression levels of VEGF-C and COX-2 and lymphatic vessel density in the lymph node metastatic group were significantly higher than in the nonmetastatic group (P < .01). A significant correlation was found between the expression levels of VEGF-C and COX-2 (r = 0.512; P < .001). COX-2 expression was significantly related to lymph node metastasis (P = .004) and VEGF-C expression (P = .005). Univariate analysis showed that survival time was impaired by higher COX-2 and VEGF-C expression levels. Multivariate survival analysis showed that COX-2 expression was an independent prognostic factor.
  
  
  CONCLUSIONS
  This study showed that VEGF-C expression was upregulated by COX-2 in OSCC. High VEGF-C expression appears to promote peritumoral lymphangiogenesis. These data indicated that lymph node metastasis is promoted by COX-2 and VEGF-C in OSCC.
authors.affiliation: Graduate Student, Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan. Electronic address: mk-oms@tokyo-med.ac.jp.
authors.forename: Michihide
authors.initials: M
authors.lastname: Kono
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.forename: Harutsugi
authors.initials: H
authors.lastname: Abukawa
authors.forename: On
authors.initials: O
authors.lastname: Hasegawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Satomi
authors.forename: Daichi
authors.initials: D
authors.lastname: Chikazu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology / Q000556:secondary*; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000502:physiology; D008207:Lymphatic Metastasis / Q000473:pathology*; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; C500987:monoclonal antibody D2-40; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human